The purpose of this project is to develop and apply ultrastructural cytochemical techniques for the study of problems in cell biology and cellular pathology. The immediate current aims are: (a) To establish the topography of cell surface moieties particularly in regard to immunoglobulins, histocompatibility antigens, and Concanavalin A binding sites on lymphocytes, melanoma cells, normal and transformed fibroblasts, macrophages and polymorphonuclear leucocytes. The behavior of these sites when treated with suitable ligands under various conditions such as variation in temperature and drug treatment is being established. Thus, the biological significance of topographical variations in various states and some aspects of the structure of the cell surface will hopefully be established. To these ends ultrastructural cytochemical techniques involving labelling of ligands with enzymes, ferritin, hemocyanin and the cytochemical demonstration of chemical entities of membranes is being developed for thin section, replication, freeze-cleavage and freeze-etching techniques. In addition ultrastructural cytochemical tracers have been and are being developed for studies of permeability barriers particularly in small blood vessels and glomeruli of normal and diseased kidneys.